高含量DHA/EPA甘油三酯促进肝脏糖原合成及其作用机制的研究

摘要

Aim To investigate the effects of high-content DHA/EPA triglyceride on hepatic glycogen synthesis and its mechanisms in diabetic mouse. Methods The diabetic mouse model was developed by feeding high fat food. The fasting plasma glucose, oral glucose tolerance, serum insulin and hepatic glycogen were assayed after feeding high-content DHA/ EPA triglyceride for 15 weeks. The mRNA expression of key genes associated with PI3K/PKB/GSK-3β insulin signal transduction pathway was detected by reverse transcription polymerase chain reaction ( RT-PCT ). Results High-content DHA/EPA triglyceride significantly decreased the level of fasting plasma glucose, reduced serum insulinemia, improved oral glucose tolerance , and increased hepatic glycogen synthesis, compared with model group ( P <0. 01 ). Meanwhile, significantly enhanced mRNA expressions of InsR, IRS-2, PI3K and PKB, and decreased GSK-3β expression were found( P <0. 01 vs model control ). And the efficacy of high-content DHA/EPA triglyceride was the best of all three fish oils tested. Conclusion The high-content DHA/EPA triglyceride could increase the hepatic glycogen synthesis and regulate the blood glucose balance by activating the pivotal genes of PI3K/ PKB/GSK-3β insulin signal transduction pathway.%目的 探究高含量DHA/EPA甘油三酯对糖尿病小鼠肝脏中糖原合成的改善作用及机制.方法 采用高脂高糖饮食诱导建立糖尿病小鼠模型.连续饲喂高含量DHA/EPA甘油三酯15周,检测其对空腹血糖、口服葡萄糖耐量、空腹血清胰岛素以及肝糖原含量的影响;采用聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)技术检测小鼠肝脏中胰岛素介导的PI3K/PKB/GSK-3β信号通路中关键基因的mRNA表达.结果 高含量DHA/EPA甘油三酯能明显降低糖尿病小鼠空腹血糖水平(P<0.01 vs 模型对照组),有效改善口服葡萄糖耐量(P<0.01 vs 模型对照组),明显降低空腹血清胰岛素水平 (P<0.01 vs 模型对照组),增加肝糖原含量(P<0.01 vs 模型对照组);同时提高肝脏中胰岛素受体(insulin receptor,InsR)、胰岛素受体底物-2(insulin receptor substrate,IRS-2)、磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)和蛋白激酶B(protein kinase B,PKB)mRNA的表达(P<0.01 vs 模型对照组),抑制糖原合成激酶-3β(glycogen synthase kinase-3β,GSK-3β) mRNA的表达(P<0.01 vs 模型对照组),且作用效果明显优于乙酯型和低含量DHA/EPA甘油三酯型鱼油.结论 高含量DHA/EPA甘油三酯通过激活胰岛素介导的PI3K/PKB/GSK-3β信号通路,促进肝糖原合成,调节血糖平衡.